Mass mortality outbreaks of Pacific oysters, Crassostrea gigas, are reported in different areas around the world affecting seriously the shellfish aquaculture sector. Two pathogens are associated with these mortality outbreaks, ostreid herpesvirus 1 (OsHV-1) and Vibrio aestuarianus. In this contexte, a better knowledge is needed in terms of oyster immunity. For this purpose, as an important degradation pathway autophagy was investigated in the Pacific oysters. An in silico research of genes involved in autophagy using the C. gigas genome allowed identification of homologs of ATG1 and ATG8/LC3(Microtubule-associated protein 1A/1B-light chain 3). Gene expression and protein detection were analysed using real-time PCR and western blot, respectively. ATG1 and ATG8 gene expression was upregulated during an experimental viral infection. Western blot analysis showed an increase of LC3 protein during the infection, suggesting an activation of autophagy. Ammonium chloride treatment was associated with increased oyster mortality whereas less mortality was reported after carbamazepine treatment in experimentally infected animals. Results suggest a protective role of autophagy against OsHV-1 and V. aestuarianus infection. This study contributes to better understand the innate immune system of Pacific oysters.